Made available in DSpace on 2014-06-12T23:15:43Z (GMT). No. of bitstreams: 2 arquivo8688_1.pdf: 335151 bytes, checksum: b21604e1cd3c64193bd83297e748fee9 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2002 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / O desequilíbrio entre células Th1 e Th2 pode ser útil em predizer o subseqüente desenvolvimento de asma. Este estudo teve como objetivo principal avaliar a existência de associação entre asma e diâmetro médio da cicatriz de BCG, e, como objetivo secundário, verificar a associação entre asma e reatividade ao teste tuberculínico. Realizou-se um estudo analítico caso-controle, onde foram selecionados crianças e adolescentes entre 6 e 14 anos. O grupo de casos (asmáticos) foi constituído por 90 indivíduos que estavam em acompanhamento no Ambulatório de Alergia e Imunologia em Pediatria do Hospital das Clínicas da UFPE ou no Ambulatório de Asma da Unidade de Pediatria Helena Moura. Apresentavam antecedente de no mínimo três episódios de dispnéia aliviados com uso de broncodilatador nos últimos doze meses ou estavam em uso de medicação profilática para asma. O outro grupo (controle) foi composto por 90 indivíduos não asmáticos (sem antecedentes pessoais de dispnéia, sibilância ou outras doenças atópicas) selecionados do Serviço de Pronto-atendimento de Pediatria do Hospital das Clínicas - UFPE. A cicatriz de BCG foi medida em seus diâmetros transverso e longitudinal e obtida uma média. O teste tuberculínico foi realizado pela técnica de Mantoux, com leitura após 72 horas. Os resultados demonstraram que asmáticos apresentam um risco 3,2 vezes maior de ter um diâmetro de cicatriz < 5mm do que não asmáticos (IC 95% = 1,40-7,63; p < 0,01). Entretanto, não houve associação estatisticamente significativa entre asma e reatividade ao teste tuberculínico (OR=1,11; IC95%=0,56-2,20; p = 0,86). Provavelmente, o diâmetro médio da cicatriz de BCG reflete uma deficiência intrínseca na produção de interferongamma, já presente nos primeiros dias de vida em crianças que possam vir a desenvolver asma. É possível que o diâmetro médio da cicatriz de BCG possa predizer o desenvolvimento de asma, porém estudos prospectivos adicionais são necessários para melhor esclarecimento dessa associação

Made available in DSpace on 2014-06-12T23:15:52Z (GMT). No. of bitstreams: 2 arquivo8706_1.pdf: 1817930 bytes, checksum: f2ac6cbb0fce841bf670e49e6225a371 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2004 / Objetivo: Revisar a literatura científica acerca do papel do interferon gama (IFN-y) na doença atópica, especificamente asma. Métodos: Pesquisados dados do Medline e Lilacs nos últimos 10 anos. Resultados: Vários autores discutem a importância da relação entre a secreção de IFN-y e o componente atópico per se, por outro lado é questionado se esta citocina tem relação direta com a doença asmática, independente do estado atópico. Foi verificada a existência de várias pesquisas relacionando asma e IFN-y; entretanto, os resultados destas pesquisas se apresentam controversos. Conclusão: Ainda não se chegou a uma conclusão definitiva do verdadeiro mecanismo de atuação desempenhado pelo IFN-y na doença asmática, é indiscutível a importância de novas pesquisas esclarecedoras sobre este assunto

The market of tobacco products presents a very specific area of fast moving consumer goods. Marketing activities are strictly limited by law and the correct establishment of communication tools is sometimes considerably difficult. In addition to the above, in the case of the tobacco industry, we are talking about almost the same product for every particular cigarette brand. My diploma thesis deals with the role of the premium brand Marlboro in the product porfolio of the company Philip Morris ČR a.s.

Since 2004 sequencing has undergone a revolutionary change with the advent of first the 454 sequencer, followed by the introduction of the Solexa/Illumina chemistries. This has led to the ability to sequence the whole genomes of a large number of microorganisms in a short space of time. Microbiology’s last revolution was in the introduction of PCR, which allowed for faster detection of pathogens, particularly viruses. With whole genome sequencing (WGS) many of the time-consuming steps carried out by a reference laboratory can be skipped. These include organism detection, speciation, antimicrobial susceptibility testing, typing and molecular epidemiology – all carried out in a single sequencing run followed by bioinformatics analysis. So far the merits of WGS in microbiology have only been demonstrated in highly specialised scientific laboratories in high-income countries. However, with continuingly decreasing costs and increasing throughput, many public health laboratories are now acquiring sequencers and their use will inevitably spread to middle-income countries. In this thesis I explore the use of WGS in three specific areas and include details on how to develop and assess bioinformatics pipelines. First, I shall demonstrate that WGS can be used to assess highly divergent regions within microorganisms by using the example of the weaknesses in current approaches to the molecular detection of methicillin-resistant Staphylococcus aureus isolates. In particular, I shall highlight how current molecular tests have limitations in detecting drug resistance when the regions of the genome conferring resistance have significant mutations. Second, I will examine how WGS can provide insights into the biology of the current vaccine against tuberculosis, Bacillus Calmette Guerin (BCG), particularly how the continued passage of the seedlot for this vaccine has led to very different versions being used around the globe. Finally, I will demonstrate how WGS can be used to develop a more targeted public health approach to tuberculosis, in particular how antimycobacterial drug resistance evolves within a population and how not all clades of Mycobacterium tuberculosis should be treated the same. Whole genome sequencing clearly has a lot to offer the fields of microbiology and communicable disease control. The next step is in translating its use into public health policy and ensuring that global approaches are unified to best benefit the populations served.

Le cancer de la vessie se caractérise par un taux de récidive de 70% après résection chirurgicale. Les tumeurs récidivantes sont traitées par une immunothérapie intravésicale au BCG dont le mode d'action est peu connu. Bien que donnant des résultats appréciables, cette thérapie est appliquée de façon empirique et reste sans effets pour 30% des patients traités. Afin d'identifier les patients réfractaires au traitement, nous avons analysé différentes caractéristiques tant au niveau des patients, de leurs tumeurs ou encore du schéma d'administration de l'immunothérapie qui seraient reliées au temps de survie sans récidive. Le système immunitaire inné, par l'intermédiaire du gène NRAMP1, est considéré comme un facteur impliqué dans l'effet antitumoral de l'immunothérapie. La distribution de plusieurs polymorphismes de ce gène a été comparée parmi différentes cohortes de patients montrant des risques variables de récidive. L'expression de l'ARNm de ce gène fut évaluée par hybridation in situ dans des spécimens de tumeurs ou par RT-PCR parmi plusieurs lignées tumorales d'origines diverses. L'analyse de l'expression d'autres antigènes fut aussi pratiquée par immunohistochimie sur des spécimens de tumeurs de patients traités au BCG. Parmi les différents marqueurs analysés, la distribution du polymorphisme D543N et la quantité de cellules tumorales exprimant l'antigène 19A211 furent associées à la survie sans récidive après immunothérapie. L'expression de NRAMP1 ne fut retrouvée dans aucune lignée cellulaire de vessie testée, même si 3 autres lignées cancéreuses (côlon et utérus) exprimaient ce gène spontanément. De plus, l'hybridation in situ a montré une expression inattendue de ce gène dans le tissu tumoral vésical. Quant au traitement d'entretien, les patients qui l'ont toléré pour au moins 1 an ont obtenu les meilleurs temps de survie sans récidive. Ainsi les résultats de ce projet semblent montrer qu'il existe des différences caractéristiques entre les patients atteints de tumeurs récidivantes et ceux traités par une simple résection transuréthrale. Ceci pourrait fournir des indications quand à pratiquer ou non une immunothérapie. / Superficial bladder cancer recurrences occur in 70% of cases. Intravesical immunotherapy is applied to prevent those recurrences but it fails in about 30% of cases. This study tried to ascertain characteristics which could be used to discriminate patients according to their recurrence risk after treatment. As the NRAMP1 gene was tied to the immune System activation, we suspected it played a role in BCG treatment efficacy. We analysed its polymorphisms distribution among patients showing variable recurrence risk and its expression in tumoral cells through in situ hybridization and RTPCR. The treatment schedule is still empirical and needs to be optimized, so we analysed the impact of long-term maintenance treatment on tumor recurrence. D543N polymorphism distribution and expression of the 19A211 antigen were significantly associated with recurrence-free survival time. Even if NRAMP1 was not found to be expressed on any bladder tumor cell lines analysed, in situ hybridization did reveal an expression of this gene mRNA in tumor cells. Moreover it was shown that patients with the best recurrence free survival time were those who tolerated maintenance treatment for at least a year. We did show that it was possible to discriminate patients through characteristics which could indicate recurrence free survival after immunotherapy.

Disertacijos objektas: įvairių BCG skiepijimo režimų įtaka tuberkulino reakcijos išraiškai, vietinei BCG žymei, specifinei serologijai, alergijos klinikai vaikams iki 6 m. Tyrime dalyvavo 509 vaikai, vakcinuoti įprasta arba pusine BCG vakcinos doze naujagimio ar 3 mėn. amžiaus. Jiems 3 mėn. po BCG vakcinacijos, 1, 2 ir 6 m. atliktas tuberkulino mėginys, įvertintas BCG randelis, ištirti specifiniai antikūnai kraujo serume, įvertintos alerginės būklės. Disertacijos išvadose konstatuojama, kad 3 mėn. amžiaus BCG vakcinuotų vaikų tuberkulino reakcijos yra stipresnės bei susidariusi vietinė BCG žymė dažnesnė, nei įprasta BCG vakcinos doze naujagimio amžiaus skiepytųjų, tiriant juos 3 mėn. po BCG vakcinacijos ar 1 m. amžiaus. Specifinių antikūnų dėsningumų nepavyko aptikti. 3 mėn. amžiaus kūdikių BCG vakcinacija sumažino su maistu siejamų alerginių bėrimų riziką mergaitėms ikimokykliniu laikotarpiu. / Object of dissertation: The influence of different BCG vaccination schedules on the tuberculin reactivity, BCG scarring, specific serology and allergy. 509 children were included in this research, all of them received BCG vaccination with standard or half dosage as newborns or 3-months old. 3 months after BCG vaccination and at one, two, and six years of age they were tested with tuberculin, and examined for BCG scarring. Anti-tuberculosis antibodies were detected in sera and children were evaluated for allergy. In conclusions of the dissertation it is declared, that 3 months after BCG vaccination and at 1 year of age children, vaccinated as 3 months - old had stronger tuberculin reactions and better BCG scarring, in comparison to neonatal vaccination. Clear consistent patterns in anti-tuberculosis antibody levels were not established. BCG vaccination at 3 months of age reduced the risk of food –related allergic rash for girls in preschool period.

Object of dissertation: The influence of different BCG vaccination schedules on the tuberculin reactivity, BCG scarring, specific serology and allergy. 509 children were included in this research, all of them received BCG vaccination with standard or half dosage as newborns or 3-months old. 3 months after BCG vaccination and at one, two, and six years of age they were tested with tuberculin, and examined for BCG scarring. Anti-tuberculosis antibodies were detected in sera and children were evaluated for allergy. In conclusions of the dissertation it is declared, that 3 months after BCG vaccination and at 1 year of age children, vaccinated as 3 months - old had stronger tuberculin reactions and better BCG scarring, in comparison to neonatal vaccination. Clear consistent patterns in anti-tuberculosis antibody levels were not established. BCG vaccination at 3 months of age reduced the risk of food –related allergic rash for girls in preschool period. / Disertacijos objektas: įvairių BCG skiepijimo režimų įtaka tuberkulino reakcijos išraiškai, vietinei BCG žymei, specifinei serologijai, alergijos klinikai vaikams iki 6 m. Tyrime dalyvavo 509 vaikai, vakcinuoti įprasta arba pusine BCG vakcinos doze naujagimio ar 3 mėn. amžiaus. Jiems 3 mėn. po BCG vakcinacijos, 1, 2 ir 6 m. atliktas tuberkulino mėginys, įvertintas BCG randelis, ištirti prieštuberkulioziniai antikūnai kraujo serume, įvertintos alerginės būklės. Disertacijos išvadose konstatuojama, kad pusine BCG vakcina skiepytųjų tuberkulino reakcijos silpnesnės, o susidariusi vietinė žymė mažesnė, o 3 mėn. BCG vakcinuotų vaikų tuberkulino reakcijos yra stipresnės, o susidariusi vietinė BCG žymė dažnesnė, nei skiepijant įprasta BCG vakcina naujagimio amžiaus vaikus lyginant su įprasta BCG vakcina naujagimio amžiaus skiepytais vaikais 3 mėn. po BCG vakcinacijos ar 1 m. vaikams. Aiškių prieštuberkuliozinių antikūnų dėsningumų nepavyko aptikti. 3 mėn. amžiaus BCG vakcinacija sumažino su maistu siejamų alerginių bėrimų riziką ikimokyklinio amžiaus mergaitėms.

Title: The Marketing Strategy for fitness center Esporta Objectives: The thesis aims to create a marketing strategy for Esporta Fitness Club. Next on the analysis of the competition it was found out, which fitness centre in exact area is the biggest threat. Finally there were completed promotional program and materials for every target group. Methods: The analysis of the competition was performed by using scoring model and the individual criteria were subsequently evaluated. Next the SWOT analysis was also prepared. There were analyzed strengths and weaknesses, opportunities and threats. Also the interviewes with selected clients of fitness center were conducted. Results: The analysis of the competition showed that the biggest threat is for Esporta Fitness Club newly opened centre Pulse Wellness and Fitness. Mainly due to the favorable price offered to its clients and a wide range of services. The interviews with longtime clients showed that four out of five of those surveyed are satisfied with the fitness center and want to continue to visit it. Only one client said that knows even better fitness center. The BCG matrix showed that Esporta Fitness Club does not have in its operation any question marks, only one dog, one star, three cash cows and one strategic unit, which is at interface of a star...

A eficácia da associação quádrupla (DPT + BCG) foi estudada através da proteção e comparação da soro conversão das vacinas, usando como adjuvante o hidróxido de alumínio e ou BCG. A potência da vacina pertussis foi avaliada pelo teste de proteção em camundongos e o BCG pelo teste de consumo de oxigênio e de vitalidade, sendo considerada satisfatória. Sendo os toxóides diftérico e tetânico considerados proteínas inertes e estáveis, suas potências não foram determinadas depois de associadas. Os níveis de anticorpos foram determinados para difteria e tétano pela reação imunoenzimática, para vacina pertussis pela reação de imunofluorescência e para o BCG pela conversão tuberculínica. Os níveis de conversão foram satisfatórios, revelando ser possível a associação sem prejuízo para nenhum dos antígenos. A associação DPT + BCG não causou reação local ou geral significante, possibilitando uma simplificação operacional. / The efficacy of the quadruple association (DPT + BCG) was studied though protection and comparison ot the conversion serum in vaccines using aluminium hydroxide or BCG as adjuvant. Both the protection power of the Pertussis vaccine evaluated by the protection test in mice and BCG by the oxygen uptake and counts of viable particles were considered satisfactory. Being difteria and tetanus toxoids considered inert and stable proteins, their protection wasn\'t determined after their combination. The antibody levels produced by the antigens were determined by the enzyme-linked immunosorbent assay to the difteria and tetanus toxoids, by the fluorescent antibody technique to the Pertussis vaccine and by the tuberculin conversion to the BCG. The conversion levels were satisfatory and there was no damage in their association. There was no meaningful local or general reaction in this association making an operational simplification possible.

Asma alérgica é uma inflamação pulmonar crônica mediada por células Th2. A Hipótese da Higiene é a teoria aceita para explicar o aumento das alergias nas últimas décadas e preconiza que a menor exposição dos indivíduos a componentes microbianos prejudica a geração mecanismos imunorregulatórios. Nosso estudo abordou a modulação da resposta alérgica pulmonar induzida por ovalbumina, por cepas de bacilo Calmette-Guérin recombinantes (rBCG) que expressam fragmentos de toxinas bacterianas. Observamos que dependendo do antígeno heterólogo expresso, a imunização intranasal com rBCG pode levar tanto a supressão como a exacerbação da resposta alérgica pulmonar. Demonstramos que tanto em um contexto profilático quanto terapêutico, rBCG é capaz de suprimir os parâmetros alérgicos, e a supressão não envolve o recrutamento de células T regulatórias, é um fenômeno local, está associada a maior produção de IFN-g do que IL-4 e é dependente de IL-12. Estes dados sugerem que a infecção pulmonar por rBCG gera um milieu capaz de bloquear a migração de células Th2 inflamatórias. / Allergic asthma is an atopic disorder mediated by Th2 cells. The Hygiene Hypothesis is the accepted theory to explain the increasing in allergy in recent deacades. It states that modern health care and hygiene practices have led to a reduced exposure to microorganisms components which impairs the generation of immunoregulatory mechanisms. The present study analysed how the intranasal infection with recombinant bacillus Calmette-Guérin (rBCG) strains expressing fragments of bacterial toxins could modulate an allergic pulmonary inflammation induced by ovalbumin. We demonstrated that the rBCG strains could supress or exacerbate the allergic inflammation depending on the expressed heterologous antigen. We analysed the effect of the mycobacterial infection in a prophylactic and in a therapeutical contexts, and we have identified that for both situations the of supression allergic features does not involve the recruitment of regulatory T cells to the lungs, is a local phenomena, is associated with an increased production of IFN-g, and is an IL-12 dependent mechanism. Taken togheter, this data suggest that the rBCG pulmonary infection generates a milieu capable to supress the chemotaxis for Th2 cells, which suppress the establishment of the allergic inflammation in the lungs.